Pyrazofurin, a potent inhibitor of orotidylate decarboxylase (ki equals 10 minus to the 9th power M), results in a marked reduction in the nucleotide pools of cytidine and uridine. Pyrazofurin, (5 times 10 minus to the 6th power M), is lethal to L12l0 and L5178Y cells in suspension culture. This effect, however, can be readily overcome by providing exogenous uridine in the culture medium. The result of providing uridine to cells exposed to Pyrazofurin is an enhanced entry of uridine into the uridine nucleotide pools. Because 5 Azacytide and 3 Deazauridine are phosphorylated by the same kinase which phospharylates uridine (uridine-cytidine kinase), it would be expected that these anti-tumor agents could be made more effective in killing cells in the presence of Pyrazofurin. With the use of L1210 and L5178Y suspension cultures and human adult leukemia cells, I propose to evaluate the entry of these two nucleoside drugs into the nucleotide pools and establish the time sequence between the inhibition of de novo pyrimidine synthesis (addition of Pyrazofurin) and the addition of these two nucleoside analogues. The nucleotide pools will be studied with the use of a high pressure liquid chromatography system which will allow a rapid method of separation and quantitation. The deoxynucleotide pools will be estimated by the DNA polymerase procedure of Solter and Handschumacher.